Proton Pump Inhibitors and EoE

Real Talk: Eosinophilic Diseases

Description:

Co-host Mary Jo Strobel, APFED’s Executive Director, is joined by co-host Holly Knotowicz, a speech-language pathologist and feeding specialist living with eosinophilic esophagitis (EoE) who serves on APFED’s Health Sciences Advisory Council. They talk with guest Dr. James Franciosi, Chief of the Division of Gastroenterology, Hepatology, and Nutrition at Nemours Children’s Health in Orlando, Florida. In this episode, Mary Jo Strobel and Holly Knotowicz interview Dr. James Franciosi about his research with proton pump inhibitors, personalized medicine, the different factors that influence the response EoE patients may have to very high dose PPI treatments and other treatments, including dietary eliminations, swallowed oral steroid medications, and for some patients, biologic medications. Dr. Franciosi explains the uses of these various treatments and compares the risks of medical treatments with the risk of untreated EoE. He also describes the potential for advances in treatment choices.

Disclaimer: The information provided in this podcast is designed to support, not replace the relationship that exists between listeners and their healthcare providers. Opinions, information, and recommendations shared in this podcast are not a substitute for medical advice. Decisions related to medical care should be made with your healthcare provider. Opinions and views of guests and co-hosts are their own.

Key Takeaways:

[:49] Co-host Mary Jo Strobel welcomes co-host Holly Knotowicz. Holly introduces the topic of proton pump inhibitors and EoE.

[1:28] Holly introduces Dr. James Franciosi, Chief of the Division of Gastroenterology, Hepatology, and Nutrition at Nemours Children’s Health in Orlando, Florida.

[1:39] Since 2008, Dr. Franciosi has cared for children and teens with eosinophilic esophagitis (EoE) and eosinophilic gastrointestinal diseases (EGIDs). His team’s mission is to reduce the symptoms of EoE and EGIDs and they have published more than 60 peer-reviewed publications.

[1:55] Holly thanks Dr. Franciosi for joining the podcast.

[2:06] Dr. Franciosi “grew up” with Beth Mays (now Beth Allen), whose family suffered from eosinophilic GI disease. When Dr. Franciosi was at the Children’s Hospital of Philadelphia (CHOP), he became very interested in eosinophilic esophagitis, which was starting to emerge as something that was different from gastroesophageal reflux.

[2:30] Dr. Franciosi had the opportunity to work with Dr. Liacouras, Dr. Spergel, and many others at CHOP. He transitioned to Cincinnati Children’s Hospital with the leadership of Dr. Marc Rothenberg, Dr. Phil Putnam, and a group trying to optimize the care for children with eosinophilic GI disease.

[3:01] Dr. Franciosi then moved to a leadership role at Nemours Children’s Health in Orlando, Florida. He has been with Nemours Children’s Health for the past 11 years. There he has done additional research in eosinophilic disease and seen many changes for the good with these conditions.

[3:37] Mary Jo notes that early in his career, Dr. Franciosi had worked with Beth Mays, now Beth Allen, who is one of the founders of APFED. Dr. Franciosi has been working with eosinophilic diseases since the time APFED was founded.

[3:56] Dr. Franciosi has conducted research into how the role of proton pump inhibitors (PPIs) in the evaluation and treatment of EoE has evolved over time. His team is very interested in what therapies may be effective for eosinophilic esophagitis (EoE) for individual patients.

[4:24] The research Dr. Franciosi has been doing for EoE and other conditions is trying to look at the right drug for the right patient, with the right dosing, etc. He calls that precision medicine or personalized medicine.

[4:39] Proton pump inhibitors (PPIs) are medications that have been around for decades. There has been an evolution of thought about whether this is a medicine that we use to define the condition of EoE or now something we can use as a treatment option.

[4:57] There have not been any randomized, placebo-controlled clinical trials for EoE using this medication and there has been a lot of variability in the literature about how well they work. That’s some of the research Dr. Franciosi has been looking into and also making sure that these are communicated as an option for the right patients with EoE.

[5:27] PPIs are traditionally thought of as blocking one of the common pathways for acid in the stomach. A proton pump in parietal cells in the GI tract pumps acid into the stomach that helps you fight bad bacteria. Sometimes the acid can cause irritation in the GI tract, the stomach, and the esophagus. The PPIs work to block those pumps.

[6:15] Over the past several decades, the thinking around EoE has evolved from it being thought to be a reflux condition that had a lot of eosinophils or allergic cells, that just didn’t get better, to being thought of as strictly different from reflux, to thinking that it may be a mix for some patients.

[6:42] As the first guidelines for EoE were developed, the initial thought was to use the PPI medications to exclude gastroesophageal reflux. In the first consensus guidelines, patients had to fail the proton pump inhibitors at a high dose to be defined as EoE. This has changed over time. In 2018 there were new guidelines with new research.

[7:15] The newer thinking is that the PPIs are not to make the diagnosis, but they’re one of several different therapies that we can use; dietary interventions and different medications, including PPIs, swallowed steroids, and some of the newer biologic medications.

[8:14] H2 blockers are some of the older medications that block acid in the stomach, but they block it in a different way. They block the histamine type-2 receptor, one of the pathways by which acid is produced in the stomach. The proton pump inhibitors block the proton pump. They’re stronger medications and they work better for acid.

[8:46] The H2RA medications have names that end in “tidine” like famotidine. The PPI medications have names that end with “azole” like pantoprazole or esomeprazole.

[9:45] EoE is a condition that we’ve learned a lot about over the past several decades. The PPI medications may have different functions. They may block the acid in the stomach; they may also have a role in reducing some of the inflammation. This led to questioning if PPIs should be used to make a diagnosis or as a choice of therapy.

[10:36] From the 1990s to the 2000 era, to the most recent guidelines in 2018, the thinking about the treatment of EoE and the use of PPIs has evolved.

[10:49] One of the important things to know is that just because you’ve been on a PPI, doesn’t mean that you’re on a high dose of PPI therapy. This is important in children and different practices.

[11:12] The general recommendation for PPI therapies is to use a high dose of PPI twice a day. For adults, that’s 40 mg of esomeprazole twice a day. For children, it’s 1 mg per kg of body weight twice a day. That’s a high dose. For some people, it may be that the medication was not used at a high dose.

[11:37] The goal ultimately is to back off the high dose and to decrease the amount of medication that’s being administered.

[11:47] Dr. Franciosi says the main surprise in his findings was that the studies in both adults and children are “all over the place.” Some people report a 30% or 20% response; other colleagues throughout the world have reported a response of about two-thirds of the patients. It was surprising to see how variable the response was.

[12:18] Dr. Franciosi thinks there is variation in the choice of PPI medications, the dosing, and how they’re administered. Dr. Franciosi and his team are also looking at how people respond to these medications. That’s where personalized medicine comes in; your genes, and factors in your body can influence how well you are responding.

[12:53] Precision medicine has been used in pediatric gastroenterology for inflammatory bowel disease with medications like 6-mercaptopurine, azathioprine, and some of the biologic medications. People can respond differently to medication. Genetic variation or other factors may create different patterns of response to the same medications.

[13:25] Precision medicine and personalized medicine are interchangeable terms.

[13:48] Before reviewing the literature for his most recent publication, Dr. Franciosi had done some genetic testing and identified that there are genetic variations that do influence how people respond or don’t respond to the PPI medications.

[14:09] We need to learn more about genetic variations. Dr. Franciosi thinks for every new diagnosis of EoE, PPIs should be considered as a medication. It’s important for patients and families to know the different options. Providers may have their own biases but they should lay out the options for their patients and families to decide.

[14:47] Dietary intervention has significant benefits for children, teens, and adults. There can be hardships with quality of life that have to be considered. Taking medication for the long term also has considerations. The newer biologic medications are a fantastic step forward but they are expensive. They are just starting to be used for EoE.

[15:21] Dr. Franciosi likes to identify to his patients that there are options in treatments: dietary elimination, proton pump inhibitors, swallowed steroids, and biologic medication for people who have strictures (narrowing) in their esophagus or fibro stenosis (scar tissue). These patients are less likely to respond to PPI medication.

[15:57] We need to do more research on this and more future prospective trials, patients with scarring are those where a different type of therapy beyond the PPI medications. Patients with inflammatory symptoms seem to respond to PPI medication.

[17:04] Dr. Franciosi’s patients and families are making some choices together. Dietary elimination may not be the right choice for certain patients but they need to have the option. Dr. Franciosi presents dietary elimination as effective for many patients. It’s an investment upfront. It presents the benefit of not using long-term medications.

[17:44] Sometimes when children have growth concerns, or the dietary interventions don’t work or are not possible, different medications may be considered.

[18:13] The benefit of using PPIs in treatment is that you can reduce the inflammation that’s occurring, alleviate symptoms and make patients feel better. There has been some debate about whether this is related to the acid primarily in the stomach and some breaks in the esophagus lining that cause antigens to go in and cause inflammation.

[18:51] Dr. Franciosi uses a balanced approach with patients and families. He tells them every treatment has risks associated with it. Also, not treating EoE has risks. He did studies at Cincinnati on what happened to patients 15 years later if they were untreated. It can involve more scar tissue, strictures, symptoms, and growth issues.

[19:37] PPIs have gotten a lot of bad press over the past few years, primarily looking at the rates of infection. When you block stomach acid, that acid is no longer there to kill bad bacteria. So there are more associated respiratory infections and stomach infections like gastroenteritis, GI bugs, etc.

[20:02] Other risks that have been talked about are dementia and kidney issues, often in older populations and patients who are generally sicker. Many people are on PPIs for general GI disorders unnecessarily. If you don’t need a drug, you shouldn’t be on it.

[20:34] The risk/benefit analysis of the infections, and other people have talked about low bone mineral density, etc., have to be balanced with the risk of untreated disease and the potential risk of other medications, as well.

[21:14] For the vast majority of patients, EoE is a chronic, long-term condition. Once you take the treatment away, whether that’s eliminating foods, or taking medication, the condition will come right back. That’s also true with proton pump inhibitors.

[21:36] The recommended approach for PPIs is a high dose of medication twice a day, to start, a repeat endoscopy after eight to 12 weeks, and come down to maintenance, which would just be once a day.

[21:55] Colleagues in Spain, who have published on this, have said about two-thirds of patients responded to the really high dose PPI medications and that among those people that respond, about two-thirds continue on maintenance and do well. Not everybody will necessarily respond or do OK with the lower dose of medication.

[22:17] In general, if you take away the medications or the treatment that you’re using, the disease will come right back and those risks of progression or scar tissue, creating strictures, and developing symptoms would return as well.

[22:39] If you are considering PPIs, ask your doctor their perspective on the different treatments that Dr. Franciosi has been discussing here. Considerations include PPIs, dietary elimination, swallowed steroid medications, and for some patients, biologic medications. Dr. Franciosi thinks biologics will become more used over the years.

[23:43] Dr. Franciosi would recommend asking a treating provider about the choice of PPI medications, the dosing that they’re planning to use, whether or not it is high-dose medication, and even what the plan is for coming down off the medication with an endoscopy or a transnasal endoscopy in eight to 12 weeks, and maintenance.

[24:03] In the U.S., high-dose PPI may not be covered by insurance. They may approve 40 mg of esomeprazole once a day but not twice a day, or make it challenging to get approved. The patients may do the second dose over the counter and Dr. Franciosi will walk them through how to do that.

[24:58] Dr. Franciosi thinks the ideal would be that patients are diagnosed with eosinophilic esophagitis and then get a cheek swab to determine their profile and what kind of response they will have using esomeprazole or if he recommends oral viscous budesonide or fluticasone. It would also be great to identify who may respond or not respond to biologic medications.

[25:37] The ideal of personalized or precision medicine is to be able to identify the right choice of treatment, including dietary approaches, for the right patient, at the right dosing.

[25:50] An underappreciated area for EoE is recognizing that we don’t have good testing to identify food reactions, allergies, etc. It would be wonderful. Allergy testing doesn’t correlate because it’s mostly IgE based. So that’s a reason for dietary elimination.

[26:38] Mary Jo and Holly thank Dr. Franciosi for participating in the podcast. Dr. Franciosi says the takeaway is that PPIs should be considered as an option for various patients.

[27:20] To learn more about eosinophilic esophagitis, visit apfed.org/eoe, apfed.org/specialists, and apfed.org/eos-connections. Holly and Mary Jo thank APFED’s education partners, linked below.

Mentioned in This Episode:

American Partnership for Eosinophilic Disorders (APFED)

APFED on YouTube, Twitter, Facebook, Pinterest, Instagram

Nemours Children’s Health

Children’s Hospital of Philadelphia

Cincinnati Children’s Hospital

Beth Allen

Real Talk: Eosinophilic Diseases Podcast

Education Partners: This episode of APFED’s podcast is brought to you thanks to the support of AstraZeneca, Bristol Myers Squibb, Sanofi, and Regeneron.

Tweetables:

“We’ve been very interested in what therapies may be effective for eosinophilic esophagitis, or EoE. The research that we’ve been doing … is trying to look at the right drug for the right patient, at the right dosing, etc.” — James Franciosi, MD

“The main benefit [of using PPIs as a treatment for EoE] is that you can reduce the inflammation that’s occurring, [and] alleviate symptoms to make patients feel better.” — James Franciosi, MD

“Once you take the treatment away, whether that’s eliminating foods, or taking medication, for the vast majority of people, the condition will come right back. That’s also true with proton pump inhibitors.” — James Franciosi, MD

Featured speaker:

Dr. James Franciosi

Gastroenterology at Nemours Children’s Health, Florida